Use of hormone replacement therapy (HRT) has increased among postmenopausal women in western countries: an estimated 20 million women worldwide were using HRT in the late 1990s. Approximately 38% of postmenopausal women in the United States use hormone replacement therapy. In 2000, 46 million prescriptions were written for Premarin (conjugated estrogens), making it the second most frequently prescribed medication in the United States and accounting for more than $1 billion in sales, and 22.3 million prescriptions were written for Prempro (conjugated estrogens plus medroxyprogesterone acetate). Prempro is currently !DA-approved for: 1) treatment of moderate-to-severe vasomotor symptoms associated with the menopause, 2) treatment of vulvar and vaginal atrophy, and 3) prevention of post-menopausal osteoporosis. Early evidence from studies of unopposed estrogen suggested that it lowered risk of cardiovascular disease, consistent with resultsfrom studies of intermediate markers that showed beneficial changes. However, recent evidence from secondary prevention trials and observational studies using combined estrogen/progestin therapy showed increased risk of coronary heart disease (CHD) in the first year. This may reflect prothrombotic and proinflammatory effects of progestins that outweigh any effects of estrogens on atherogenesis and vasodilatation. Hippokratia 2002, 6 (2): 51-56